Arterial Stiffness in the Heart Disease of CKD

CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (, uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD

Segmentation of whole cells and cell nuclei from 3-D optical microscope images using dynamic programming

金沢大学医薬保健研究域医学系Communications between cells in large part drive tissue development and function, as well as disease-related processes such as tumorigenesis. Understanding the mechanistic bases of these processes necessitates quantifying specific molecules in adjacent cells or cell nuclei of intact tissue. However, a major restriction on such analyses is the lack of an efficient method that correctly segments each object (cell or nucleus) from 3-D images of an intact tissue specimen. We report a highly reliable and accurate semi-automatic algorithmic method for segmenting fluorescence-labeled cells or nuclei from 3-D tissue images. Segmentation begins with semi-automatic, 2-D object delineation in a user-selected plane, using dynamic programming (DP) to locate the border with an accumulated intensity per unit length greater that any other possible border around the same object. Then the two surfaces of the object in planes above and below the selected plane are found using an algorithm that combines DP and combinatorial searching. Following segmentation, any perceived errors can be interactively corrected. Segmentation accuracy is not significantly affected by intermittent labeling of object surfaces, diffuse surfaces, or spurious signals away from surfaces. The unique strength of the segmentation method was demonstrated on a variety of biological tissue samples where all cells, including irregularly shaped cells, were accurately segmented based on visual inspection. © 2006 IEEE

Clinical Features of Cardio-Renal Syndrome in a Cohort of Consecutive Patients Admitted to an Internal Medicine Ward

Introduction: Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward. Patients and Methods: We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFRMDRD186, GFRMDRD175), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault. Results: Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m2. GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m2. Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis. Conclusions: CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR

Factors affecting body temperatures of toads

Factors influencing levels and rates of variation of body temperature ( T b ) in montane Bufo boreas boreas and in lowland Bufo boreas halophilus were investigated as an initial step toward understanding the role of natural thermal variation in the physiology and energetics of these ectothermic animals. Body temperatures of boreas can vary 25–30° C over 24-h periods. Such variation is primarily due to both nocturnal and diurnal activity and the physical characteristics of the montane environment. Bufo boreas halophilus are primarily nocturnal except during breeding and are voluntarily active at body temperatures ranging between 10 and 25° C. Despite variation in T b encountered in the field, boreas select a narrow range of T b in a thermal gradient, averaging 23.5 and 26.2° C for fasted individuals maintained under field conditions or acclimated to 20° C, respectively. In a thermal gradient the mean T b of fasted halophilus acclimated to 20° C is 23.9° C. Skin color of boreas varies in the field from very dark to light. The dark skins absorb approximately 4% more radiation than the light ones. Light colored boreas should absorb approximately 5% more radiation than similarly colored halophilus . Evaporative water losses increase directly with skin temperatures and vapor pressure deficit in both subspecies. Larger individuals heat and cool more slowly than smaller ones. Calculation of an enery budget for boreal toads suggests that they could sit in direct sunlight for long periods without fatally overheating, providing the skin was continually moist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47722/1/442_2004_Article_BF00344732.pd

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

One-dimensional nonlinear model for predication of crack spacing in concrete pavements

This paper proposes a one-dimensional non-linear model lo predict the minimum and maximum crack spacings due to shrinkage in concrete pavements. The proposed model consists of two cohesive cracks and an elastic bar restrained by distributed elastic springs. The cohesive crack is characterized by an exponential softening constitutive relation. A set of non-linear equilibrium conditions are obtained. By varying the length of the elastic bar of the proposed model, the tensile forces acting on the cohesive cracks and the energy profiles are investigated. It is demonstrated that the cracking pattern varies with the length of the elastic bar (i.e. the spacing between the two possible cracks), from which the minimum and maximum crack spacings are obtained. Numerical analyses are made of a model pavement and the results indicate that it is the energy minimization principle that governs the cracking pattern. The proposed model provides physical insight into the mechanism of crack spacing in concrete pavements